Inhibition of active bone resorption by copper

Abstract

An investigation of the role of copper in bone metabolism was undertaken. Explanted calvaria from 6-day-old mice were grown for 48 h in medium with and without the addition of copper sulfate. Active resorption was found to be significantly inhibited in the presence of copper sulfate concentrations of 10(-6)M and above. Copper sulfate concentrations of 10(-5)M and above inhibited hydroxyproline, protein, and DNA synthesis. Lower concentrations wee ineffective. The effect of 5 X 10(-6)M copper sulfate on resorption was reversible. Several other compounds were tested for similar effects and at 5 X 10(-6)M were found to inhibit bone resorption in the order: copper sulfate greater than brown gold chloride greater than sodium aurothiomalate greater than zinc sulfate greater than sodium sulfate. The copper sulfate effect was twice that of sodium aurothiomalate, and sodium sulfate was not significantly inhibitory. The results suggest that the high serum copper levels associated with rheumatoid arthritis may reflect the activity of a hypothetical control mechanism of bone resorption. In the diseased state this would act to restore the normal rate of bone resorption.

Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males

“…However, reduced lysyl oxidase activity with consequent reduction in collagen crosslinking does not readily explain the increased excretion of pyridinium crosslinks observed in the present study. Our results, taken together with the evidence from in vitro studies (Wilson et al, 1981;Katz et al, 1984) suggests that increased bone resorption may also contribute to the demineralisation of bone seen in Cu de®ciency. EatonEvans et al, (1996) have suggested that reduced activity of other Cu ± dependent enzymes for example, superoxide dismutase and cytochrome c oxidase, could be involved in the abnormalities of bone seen in Cu de®ciency.…”

“…An increased rate of bone resorption has been suggested as one explanation for the reduced bone mass observed in Cu-de®cient rats (Strause et al, 1986). Furthermore, studies carried out in vitro have shown that Cu reduces active bone resorption, as measured by release of 45 Ca or hydroxyproline into the bathing medium from cultured explanted 45 Ca-labelled mouse calvaria bone grown in medium with or without the addition of Cu (Wilson et al, 1981;Katz et al, 1984). The concentration of Cu used in media in these in vitro studies corresponded to physiological concentrations of Cu found in experimental mice.…”

Effects of Copper on Bone Component in the Femoral Tissues of Rats: Anabolic Effect of Zinc Is Weakened by Copper

“…Copper has been shown to inhibit active bone resorption in cultured explanted mouse calvaria bones in vitro. 19) Copper may have a suppressive effect on bone resorption. In addition, copper has been shown to inhibit osteoclastogenesis in a bone marrow culture system in vitro.…”

No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status

“…An increased rate of bone resorption has been suggested as one explanation for the reduced bone mass observed in Cu-de®cient rats (Strause et al, 1986). Furthermore, studies carried out in vitro have shown that Cu reduces active bone resorption, as measured by release of 45 Ca or hydroxyproline into the bathing medium from cultured explanted 45 Ca-labelled mouse calvaria bone grown in medium with or without the addition of Cu over a 48 h period (Wilson et al, 1981;Katz et al, 1984). The concentration of Cu used in media in these in vitro studies corresponded to physiological concentrations of Cu found Dietary Cu supplementation and bone biomarkers KD Cashman et al in experimental mice.…”

“…The concentration of Cu used in media in these in vitro studies corresponded to physiological concentrations of Cu found Dietary Cu supplementation and bone biomarkers KD Cashman et al in experimental mice. Wilson et al (1981) suggested, based on their in vitro data, that a higher Cu concentration, but within the physiological range, reduces bone resorption.…”